Azacycloalkane derivatives as inhibitors of stearoyl-coenzyme a delta-9 desaturase

A compound of structural formula I:

• or a pharmaceutically acceptable salt thereof;
• wherein
• each m is independently an integer from 0 to 4;
• each n is independently an integer from 0 to 2;
• each s is independently an integer from 1 to 3;
• each t is independently an integer from 1 to 3;
• q is 0 or 1;
• r is 0 or 1;
• Z is O, S, or NR4;
• X—Y is N—CRaRb, CR14—S(O)0-2, or CR13—CRaRb;
• W is heteroaryl selected from the group consisting of:
• Ar is phenyl, naphthyl, or heteroaryl optionally substituted with one to five R3 substituents;
• Ra and Rb are each independently hydrogen or C1-3 alkyl, wherein alkyl is optionally substituted with one to three substituents independently selected from fluorine and hydroxy;
• R1 is heteroaryl selected from the group consisting of:
• wherein Rc is —(CH2)mCO2H, —(CH2)mCO2C1-3 alkyl, —(CH2)m-Z-(CH2)pCO2H, or —(CH2)m-Z-(CH2)pCO2C1-3 alkyl, wherein each (CH2) methylene group is optionally substituted with one or two substituents selected from the group consisting of C1-4 alkyl, fluorine, oxo, and hydroxy;
• and wherein said R1 heteroaryl ring is optionally substituted with one substituent independently selected from the group consisting of cyano, halogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkylthio, C1-4 alkylsulfonyl, and trifluoromethyl;
• each R2 is independently selected from the group consisting of:
• hydrogen,
• halogen,
• hydroxy,
• cyano,
• amino,
• nitro,
• C1-4 alkyl, optionally substituted with one to five fluorines,
• C1-4 alkoxy, optionally substituted with one to five fluorines,
• C1-4 alkylthio, optionally substituted with one to five fluorines,
• C1-4 alkylsulfonyl,
• carboxy,
• C1-4 alkyloxycarbonyl, and
• C1-4 alkylcarbonyl;
• each R3 is independently selected from the group consisting of:
• C1-6 alkyl,
• C2-6 alkenyl,
• (CH2)n-phenyl,
• (CH2)n-naphthyl,
• (CH2)n-heteroaryl,
• (CH2)n-heterocyclyl,
• (CH2)nC3-7 cycloalkyl,
• halogen,
• nitro,
• (CH2)nOR4,
• (CH2)nN(R4)2,
• (CH2)nC≡N,
• (CH2)nCO2R4,
• (CH2)nNR4SO2R4
• (CH2)nSO2N(R4)2,
• (CH2)nS(O)O0-2R4,
• (CH2)nNR4C(O)N(R4)2,
• (CH2)nC(O)N(R4)2,
• (CH2)nNR4C(O)R4,
• (CH2)nNR4CO2R4,
• (CH2)nC(O)R4,
• O(CH2)nC(O)N(R4)2,
• (CH2)s-Z-(CH2)t-phenyl,
• (CH2)s-Z-(CH2)t-naphthyl,
• (CH2)s-Z-(CH2)t-heteroaryl,
• (CH2)s-Z-(CH2)t-heterocyclyl,
• (CH2)s-Z-(CH2)t—C3-7 cycloalkyl,
• (CH2)s-Z-(CH2)t—OR4,
• (CH2)s-Z-(CH2)t—N(R4)2,
• (CH2)s-Z-(CH2)t—NR4SO2R4,
• (CH2)s-Z-(CH2)t—C≡N,
• (CH2)s-Z-(CH2)t—CO2R4,
• (CH2)s-Z-(CH2)t—SO2N(R4)2,
• (CH2)s-Z-(CH2)t—S(O)0-2R4,
• (CH2)s-Z-(CH2)t—NR4C(O)N(R4)2,
• (CH2)s-Z-(CH2)t—C(O)N(R4)2,
• (CH2)s-Z-(CH2)t—NR4C(O)R4,
• (CH2)s-Z-(CH2)t—NR4CO2R4,
• (CH2)s-Z-(CH2)t—C(O)R4,
• CF3,
• CH2CF3,
• OCF3, and
• OCH2CF3;
• in which phenyl, naphthyl, heteroaryl, cycloalkyl, and heterocyclyl are optionally substituted with one to three substituents independently selected from halogen, hydroxy, C1-4 alkyl, trifluoromethyl, and C1-4 alkoxy;
• and wherein any methylene (CH2) carbon atom in R3 is optionally substituted with one to two groups independently selected from fluorine, hydroxy, and C1-4 alkyl;
• or two substituents when on the same methylene (CH2) group are taken together with the carbon atom to which they are attached to form a cyclopropyl group;
• each R4 is independently selected from the group consisting of
• hydrogen,
• C1-6 alkyl,
• (CH2)n-phenyl,
• (CH2)n-heteroaryl,
• (CH2)n-naphthyl, and
• (CH2)nC3-7 cycloalkyl;
• wherein alkyl, phenyl, heteroaryl, and cycloalkyl are optionally substituted with one to three groups independently selected from halogen, trifluoromethyl, C1-4 alkyl, and C1-4 alkoxy;
• or two R4 groups together with the atom to which they are attached form a 4- to 8-membered mono- or bicyclic ring system optionally containing an additional heteroatom selected from O, S, NH, and NC1-4 alkyl;
• R5, R6, R7, R8, R9, R10, R11, and R12 are each independently hydrogen, fluorine, or C1-3 alkyl, wherein alkyl is optionally substituted with one to three substituents independently selected from fluorine and hydroxy;
• R13 is hydrogen, C1-3 alkyl, fluorine, or hydroxy;
• and
• each R14 is hydrogen or C1-3 alkyl.